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Research Letters |

ω-3 Long-Chain Polyunsaturated Fatty Acid Intake Inversely Associated With 12-Year Progression to Advanced Age-Related Macular Degeneration FREE

John Paul SanGiovanni, ScD; Elvira Agrón, MA; Traci E. Clemons, PhD; Emily Y. Chew, MD
Arch Ophthalmol. 2009;127(1):109-116. doi:10.1001/archophthalmol.2008.518.
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Published online

Age-related macular degeneration (AMD) is a leading cause of vision loss. Age-Related Eye Disease Study (AREDS) participants reporting the highest intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFAs) were approximately half as likely as their peers reporting the lowest intake of these nutrients to have neovascular (NV) AMD1 at baseline or to progress across a 6-year period from bilateral drusen to central geographic atrophy (CGA).2 The Age-Related Eye Disease Study provides data that represent, to our knowledge, the largest longitudinal sample collected and classified with standardized methods as part of a natural history study on AMD. We now report that our baseline and 6-year findings persisted in 12-year AMD incidence models. These results are consistent with existing data.3,4

The Age-Related Eye Disease Study was a National Institutes of Health–sponsored and administered multicenter study designed to assess the clinical course, prognosis, and risk factors of AMD (http://www.nei.nih.gov/amd/). We examined the relationship of dietary intake of ω-3 LCPUFAs with progression to advanced AMD in 1837 AREDS participants who had a moderate risk for developing sight-threatening AMD (1211 participants in category 3a and 626 participants in category 4a). Participants in category 3a had bilateral visual acuity of 20/32 or better and bilateral large (≥125-μm) drusen, extensive intermediate drusen, and/or geographic atrophy that did not involve the center of the macula in at least 1 eye. Category 4a participants had visual acuity of 20/32 or better and no advanced AMD (geographic atrophy involving the center of the macula or features of NV AMD) in the study eye; the fellow eye had definite lesions of advanced AMD. Category 3b and 4b participants had visual acuity worse than 20/32. In AREDS report No. 1,5 we described outcome ascertainment for CGA and NV AMD from centralized grading of annual stereoscopic fundus color photographs; participants progressing to CGA and/or NV AMD in their study eye(s) were classified with incident advanced AMD. We estimated dietary intake with a validated semiquantitative food frequency questionnaire developed for AREDS.1,2 Nutrient density values at baseline defined the LCPUFA variables.1 We computed odds ratios in repeated-measures logistic regression models incorporating generalized estimating equation methods. This permitted determination of advanced AMD at each visit for each participant. All of the models included terms for baseline age (<65 vs 65-69 and ≥70 years), sex, smoking status at diagnosis (never, past, or current), total energy intake (modeled as a continuous variable), AREDS treatment (placebo vs zinc, antioxidants, and zinc plus antioxidants), and baseline AMD status (AREDS category 3a vs 4a).

Participants reporting the highest baseline consumption of ω-3 LCPUFAs were approximately 30% less likely than their peers reporting the lowest ω-3 LCPUFA consumption to develop advanced AMD by the end of the 12-year follow-up period (Table). Results for CGA and NV AMD were similar; respective multivariate odds ratios were 0.65 (95% confidence interval, 0.45-0.92; P ≤ .02) and 0.68 (95% confidence interval, 0.49-0.94; P ≤ .02).

Table Graphic Jump LocationTable. Odds Ratios for 12-Year Progression to Advanced Age-Related Macular Degenerationa

ω-3 LCPUFAs and their metabolites have the capacity to act on processes implicated in AMD pathogenesis.3 Although inferences are constrained by the observational nature of our research designs (frequent consumption of ω-3 LCPUFA–rich foods may be a proxy for exposure to unmeasured environmentally or behaviorally based protective factors), biologically credible explanations for relationships between ω-3 LCPUFAs and AMD now exist in studies applying in vivo6,7 and in vitro8 model systems. The findings from these basic studies strengthen conclusions from extant observational studies (reviewed by SanGiovanni and Chew3 and Chong et al4) regarding the association of ω-3 LCPUFA intake with AMD. Because the concentration of retinal ω-3 LCPUFAs is modifiable by and dependent on dietary composition, these nutrients may represent an easily implemented approach to modifying risk of AMD progression; we are now conducting a 5-year, 4000-person clinical trial to examine this issue of public health significance (http://www.areds2.org).

ARTICLE INFORMATION

Correspondence: Dr SanGiovanni, Clinical Trials Branch, National Eye Institute, 10 Center Dr, CRC, MSC 1204, Bethesda, MD 20892-1204 (jpsangio@post.harvard.edu).

Author Contributions: Dr SanGiovanni had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: None reported.

Funding/Support: This study was supported by contracts from the National Eye Institute, National Institutes of Health, Bethesda, Maryland.

Role of the Sponsor: This project was developed in the AREDS Project Office and the AREDS Coordinating Center, Intramural Branch, National Eye Institute, National Institutes of Health.

Additional Contributions: Members of the AREDS Operations Committee (Roy C. Milton, PhD, Robert D. Sperduto, MD, Anne S. Lindblad, PhD, Gary G. Gensler, MS, Alice K. Henning, MS, Natalie Kurinij, PhD, and Frederick L. Ferris, MD) offered helpful concept and technical reviews on nutrient-based articles in AREDS.

SanGiovanni  JPChew  EYClemons  TE  et al. Age-Related Eye Disease Study Research Group, The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS report No. 20. Arch Ophthalmol 2007;125 (5) 671- 679
PubMed Link to Article
SanGiovanni  JPChew  EYAgrón  E  et al. Age-Related Eye Disease Study Research Group, The relationship of dietary ω-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report No. 23. Arch Ophthalmol 2008;126 (9) 1274- 1279
PubMed Link to Article
SanGiovanni  JPChew  EY The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res 2005;24 (1) 87- 138
PubMed Link to Article
Chong  EWKreis  AJWong  TYSimpson  JAGuymer  RH Dietary ω-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis. Arch Ophthalmol 2008;126 (6) 826- 833
PubMed Link to Article
Age-Related Eye Disease Study Research Group, The Age-Related Eye Disease Study (AREDS): design implications: AREDS report No. 1. Control Clin Trials 1999;20 (6) 573- 600
PubMed Link to Article
Connor  KMSanGiovanni  JPLofqvist  C  et al.  Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 2007;13 (7) 868- 873
PubMed Link to Article
Koto  TNagai  NMochimaru  H  et al.  Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice. Invest Ophthalmol Vis Sci 2007;48 (9) 4328- 4334
PubMed Link to Article
Mukherjee  PKMarcheselli  VLBarreiro  SHu  JBok  DBazan  NG Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling. Proc Natl Acad Sci U S A 2007;104 (32) 13152- 13157
PubMed Link to Article

Figures

Tables

Table Graphic Jump LocationTable. Odds Ratios for 12-Year Progression to Advanced Age-Related Macular Degenerationa

References

SanGiovanni  JPChew  EYClemons  TE  et al. Age-Related Eye Disease Study Research Group, The relationship of dietary lipid intake and age-related macular degeneration in a case-control study: AREDS report No. 20. Arch Ophthalmol 2007;125 (5) 671- 679
PubMed Link to Article
SanGiovanni  JPChew  EYAgrón  E  et al. Age-Related Eye Disease Study Research Group, The relationship of dietary ω-3 long-chain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report No. 23. Arch Ophthalmol 2008;126 (9) 1274- 1279
PubMed Link to Article
SanGiovanni  JPChew  EY The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina. Prog Retin Eye Res 2005;24 (1) 87- 138
PubMed Link to Article
Chong  EWKreis  AJWong  TYSimpson  JAGuymer  RH Dietary ω-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis. Arch Ophthalmol 2008;126 (6) 826- 833
PubMed Link to Article
Age-Related Eye Disease Study Research Group, The Age-Related Eye Disease Study (AREDS): design implications: AREDS report No. 1. Control Clin Trials 1999;20 (6) 573- 600
PubMed Link to Article
Connor  KMSanGiovanni  JPLofqvist  C  et al.  Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis. Nat Med 2007;13 (7) 868- 873
PubMed Link to Article
Koto  TNagai  NMochimaru  H  et al.  Eicosapentaenoic acid is anti-inflammatory in preventing choroidal neovascularization in mice. Invest Ophthalmol Vis Sci 2007;48 (9) 4328- 4334
PubMed Link to Article
Mukherjee  PKMarcheselli  VLBarreiro  SHu  JBok  DBazan  NG Neurotrophins enhance retinal pigment epithelial cell survival through neuroprotectin D1 signaling. Proc Natl Acad Sci U S A 2007;104 (32) 13152- 13157
PubMed Link to Article

Correspondence

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